Bordetella pertussis, the microorganism which causes the disease commonly known as whooping cough, produces several toxins (i.e. pertussis toxin (PT) and dermonecrotic toxin (DNT) which appear to play important pathogenic roles. Conditions have been developed which permit rapid and efficient isolation of PT toxin in sufficient quantities to permit structural and physiologic studies. The toxin was shown to catalyze covalent modification (by ADP-ribosylation) of a protein present in the cell membrane. Further studies demonstrated that the substrate polypeptide plays an important role in the regulation of adenylate cyclase. Studies with a variety of cell types including adipocytes and lymphoma cell line S49 cyc- cells, among others, demonstrate that the ADP ribosylated polypeptide is involved in the coupling of inhibitory stimuli to the negative modulation of the adenylate cyclase catalytic subunit. Highly purified, but not homogeneous, preparations of dermonecrotic toxin have been obtained. Preliminary data suggest that the action of this toxin is complicated and may require the concurrent presence of several polypeptides.